chr17-1725296-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001163809.2(WDR81):​c.337C>T​(p.Arg113Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 1,547,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

WDR81
NM_001163809.2 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22
Variant links:
Genes affected
WDR81 (HGNC:26600): (WD repeat domain 81) This gene encodes a multi-domain transmembrane protein which is predominantly expressed in the brain and is thought to play a role in endolysosomal trafficking. Mutations in this gene are associated with an autosomal recessive form of a syndrome exhibiting cerebellar ataxia, cognitive disability, and disequilibrium (CAMRQ2). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27711037).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR81NM_001163809.2 linkuse as main transcriptc.337C>T p.Arg113Trp missense_variant 1/10 ENST00000409644.6 NP_001157281.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR81ENST00000409644.6 linkuse as main transcriptc.337C>T p.Arg113Trp missense_variant 1/101 NM_001163809.2 ENSP00000386609 P1Q562E7-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000675
AC:
1
AN:
148092
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
79810
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000358
AC:
5
AN:
1395240
Hom.:
0
Cov.:
75
AF XY:
0.00000436
AC XY:
3
AN XY:
688236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000316
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.27e-7
Gnomad4 OTH exome
AF:
0.0000517
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152264
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 23, 2023The c.337C>T (p.R113W) alteration is located in exon 1 (coding exon 1) of the WDR81 gene. This alteration results from a C to T substitution at nucleotide position 337, causing the arginine (R) at amino acid position 113 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.28
T
MetaSVM
Benign
-0.56
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
1.0
D;D;D;D;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-2.9
D
REVEL
Benign
0.12
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.0050
D
Vest4
0.38
MutPred
0.50
Loss of disorder (P = 0.0079);
MVP
0.61
MPC
0.96
ClinPred
0.78
D
GERP RS
4.9
Varity_R
0.13
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1023271817; hg19: chr17-1628590; API